Experiments outlined in this proposal focus on mechanisms regulating dopamine-B-hydroxylase (DBH), a key enzyme in catecholamine biosynthesis, and their relevence to adaption and behavioral function. DBH activity and concentration are responsive to diverse stimuli; changes in enzyme activity reflect the organism's attempt to adapt to a stimulus, and are mediated by biochemical regulatory mechanisms. We have evidence that changes in DBH are governed by a rich array of variables; stimulus- and genetically-determined variables will be considered in this proposal. In a given inbred rat strain, different stimuli cause quite different changes in DBH activity. Further, the same stimulus can produce opposite responses in different strains. Interactions between 3 stimuli (cold exposure, immobilization, electric footshock) and 7 inbred rat strains (LEW, WF, F344, BUF, BN, ACI, MAXX) will be studied in 3 phases. First, DBH responses will be analyzed descriptively between stimuli and strains. We will assess DBH activity (in vivo and in vitro procedures to be used) as well as enzyme protein concentration (using immunologic procedures) in brain and peripheral tissues to define the nature and direction of change. Second, mechanisms responsible for DBH changes in 2 inbred strains will be determined. Potential changes in physicochemical properties of DBH, "endogenous inhibitor" concentration, axoplasmic transport, enzyme protein synthesis and DBH degradation will be assessed. These studies will include formal genetic analysis, and a comparison of sex differences. Third, behavioral relevance of these responses will be explored using inbred and hybrid rat strains. The final portion of this proposal will begin extending our analysis into clinical populations. We will determine whether serum DBH activity in man correlates with anxiety, and whether pharmacologic treatment of symptoms is accompained by parallel changes in enzyme activity.